Sun Yat-Sen Cancer Center Research Articles

Pei-Rong Ding, MD, PhD.

Dr. Pei-Rong Ding is a Professor of Surgery and Attending Physician at Sun Yat-Sen Cancer Center in Guangzhou, China. He was born and raised in Chaozhou (i.e., Teochew) City, an ancient city with a rich culture in southern China. He obtained both his undergraduate and medical degrees from Sun Yat-Sen University in Guangzhou, China. Along the way, he served as a research fellow at Memorial Sloan Kettering Cancer Center from 2009 to 2010, focusing on colorectal cancer—something that has carried his interests through his entire career. Since then, he has developed a particular niche within colorectal cancer, focusing on helping families who suffer from hereditary colorectal cancer, and reducing their prognosis and minimizing their family risk. He has also set up both a fund as well as a registry focusing on this aspect.

Therapeutic Drug Monitoring of Busulfan in Patients Undergoing Hematopoietic Cell Transplantation: A Pilot Single-Center Study in Taiwan.

Busulfan has been used as a conditioning regimen in allogeneic hematopoietic cell stem transplantation (HSCT). Owing to a large inter-individual variation in pharmacokinetics, therapeutic drug monitoring (TDM)-guided busulfan dosing is necessary to reduce graft failure and relapse rate. As there exists no TDM of busulfan administration for HCT in Taiwan, we conducted a pilot study to assess the TDM-dosing of busulfan in the Taiwanese population; Seven patients with HCT from The Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan, received conditioning regimens consisting of intravenous busulfan and other chemotherapies. After the initial busulfan dose, blood samples were collected for busulfan TDM at 5 min, 1 h, 2 h, and 3 h. Busulfan was extracted and detected by performing stable-isotope dilution LC–MS/MS. Plasma busulfan concentration was quantified and used for dose adjustment. Potential adverse effects of busulfan, such as mucositis and hepatic veno-occlusive disease (VOD), were also evaluated; The LC–MS/MS method was validated with an analyte recovery of 88–99%, within-run and between-run precision of <15%, and linearity ranging from 10 to 10,000 ng/mL. Using TDM-guided busulfan dosing, dose adjustment was necessary and performed in six out of seven patients (86%) with successful engraftments in all patients (100%). Mild mucositis was observed, and VOD was diagnosed in only one patient; This single-center study in Taiwan demonstrated the importance of busulfan TDM in increasing the success rate of HCT transplantation. It is also necessary to further investigate the optimal busulfan target value in the Taiwanese population in the future.

Cutaneous extranodal natural killer (NK) / T - cell lymphoma: A comprehensive clinical features and outcomes analysis of 71 cases

BackgroundThe skin is the common extranasal sites in extranodal natural killer (NK) / T - cell lymphoma, (ENKTL). However, data regarding cutaneous ENKTL are relatively scarce. Thus, we performed a large retrospective study to analyze clinical features and treatment outcomes of cutaneous ENKTL. Patients and methodsSeventy-one patients with cutaneous ENKTL newly diagnosed between 2001 and 2018 were retrospectively analyzed from Sun Yat-sen cancer center. ResultsThe median overall survival (OS) was 15.5 months (95 % confidence interval: 8.0–22.1 months). Age, treatment strategy, and treatment response were independent prognostic factors for cutaneous ENKTL. Patients who could undergo chemotherapy followed by radiotherapy showed a significantly better survival than those treated with chemotherapy alone (p < 0.001). The 3 - year OS rates were 73.9 % for patients who achieved complete response (CR) compared with 10.3 % for patients who did not (p < 0.001). ConclusionWe reported by far the largest series of cutaneous ENKTL, and demonstrated its aggressive clinical behavior and unsatisfying response to the current therapeutic strategies. Further investigations are required for the better understanding and management of this uncommon disease.

Abstract P2-08-56: Effects of young age on prognosis in patients with node-negative tumors 2 cm or smaller breast cancer

Abstract Background It is still controversial to consider age as a prognostic factor into the treatment strategy of patients with T1N0M0 breast cancer. Aim The main purpose of this study was to evaluate the effect of age on recurrence risk in patients diagnosed with T1N0M0 breast cancer as well as compare the prognosis of young aged patients(YA,≤40 years old) to non-young aged patients(non-YA,&amp;gt;40 years old) by using a propensity score matching(PSM) analysis. Methods 365 patients with T1N0M0 breast cancer diagnosed between 2003 and 2016 who received surgery in Sun Yat-sen Memorial Hospital Breast Cancer Center were included.The recurrence free survival (RFS) and risk factors for recurrence were identified by using Kaplan-Meier method and Cox proportional hazards models. PSM was then used to reduce the confounding effect of known risk factors on prognosis and then to compare 5-year RFS rates in patients between two age groups. Results After a median follow up of 79 months, 54 patients developed recurrences and 5-year RFS was 87.6%. YA patients had lower RFS estimates (80.6%), compared to patients diagnosed in a later age (89.1% if older than 40-years old; P = 0.049). YA patients tended to have Her-2 positive, TNBC tumors, higher rate of Ki-67 expression and nuclear grade tumor. At multivariate analysis, Her-2 positive (HR 2.115; 95% CI 1.103-4.055, p=0.024) and TNBC (HR 2.963; 95% CI 1.485-5.914, p=0.002) resulted independent prognostic factors of patient with T1N0M0 breast cancer. In the subgroup analysis, we found significant poor RFS for YA patients with Her-2 positive breast cancer compared to the older counterparts(p=0.006) and YA patients were associated with significantly higher rates of the locoregional recurrence rather than metastasis(p=0.004), especially in first 5 years after diagnosis. After PSM, the baseline level and treatment status including tumor size, grade, HR status, Her-2 status, Ki67 expression breast surgery type and systemic adjuvant treatment(AST) of patients in the two age groups tended to be equal. As result, we found significant difference in the 5-year RFS between two age groups(p=0.008). Conclusion Based on equal treatment condition, young age at presentation conferred a worse prognosis in patients with T1N0M0 breast cancer is independent on other pathological features. Citation Format: Zhong W, Tan L, You N, Wang Y, Liang G, Liu Z, Ling Y, Tian Z, Gong C. Effects of young age on prognosis in patients with node-negative tumors 2 cm or smaller breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-56.

Protein Arginine Methyltransferase 3-Induced Metabolic Reprogramming Is a Vulnerable Target of Pancreatic Cancer

Background: The biological function of protein arginine methyltransferase 3 (PRMT3) is not well known because very few physiological substrates of PRMT3 have been identified to date. Methods: The clinical significance of PRMT3 in pancreatic cancer was studied by database analysis. The PRMT3 protein level in human pancreatic tumors was detected by immunoblotting. PRMT3-associated proteins and the methylation sites on the proteins were investigated using mass spectrometry. Capillary electrophoresis time-of-flight mass spectrometry and seahorse bioscience were performed to analyze metabolic reprogramming. Combination index analysis and xenograft animal model were conducted to explore the effects of combination of inhibitors of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and oxidative phosphorylation on tumor growth. Findings: We find the expression of PRMT3 is upregulated in pancreatic cancer, and its expression is associated with poor survival. We further demonstrate that GAPDH is methylated at R248 by PRMT3 in vivo. The methylation of GAPDH by PRMT3 enhances its catalytic activity while the mutation of R248 abolishes the effect. In cells, PRMT3 overexpression triggers metabolic reprogramming and enhances glycolysis and mitochondrial respiration simultaneously in a GAPDH-dependent manner. PRMT3-overexpressing cancer cells are addicted to GAPDH-mediated metabolism and sensitive to the inhibition of GAPDH and mitochondrial respiration. The combination of inhibitors of GAPDH and oxidative phosphorylation induces a synergistic inhibition on cellular growth in vitro and in vivo. Interpretation: Our results suggest PRMT3-induced metabolic reprogramming is a vulnerable target of pancreatic cancer. Funding Statement: This work was supported by the grants from the Ministry of Science and Technology (MOST-103-2314-B-037-075; MOST-104-2314-B-037-004; MOST-105-2314-B-037-001; MOST-107-2320-B-400-006-MY3 to M.-R.P. and W.-C.H. and MOST-106-2321-B-400-007 to L.-T.C.). This study was also supported by the grant from National Research Institutes (NHRI-107A1-CACO-02181811 to Y.-S.S.) and the Yen-Hsu Education Foundation to W.-C.H. Declaration of Interests: The authors have no conflicts of interest to declare. Ethics Approval Statement: Human pancreatic tumor tissues were obtained from patients undergoing surgical resection at Koo Foundation Sun Yat-Sen Cancer Center (Taipei, Taiwan) and National Cheng Kung University Hospital (Tainan, Taiwan) under the guidelines approved by the Institution Review Board at National Health Research Institutes. Written informed consent was obtained from each patient. All animal experiments were approved by Animal Care Committee of National Health Research Institutes.

Post-Mastectomy Radiation Therapy in Stage II N1 Breast Cancer Patients Is Associated with Improved Survival with Different Sub-Type

Post-operative radiotherapy (PMRT) has shown to reduce locoregional recurrence and increase disease-free survival and overall survival in high risk breast cancer patients, in combination with chemotherapy or hormone therapy. For stage II breast cancer, PMRT was still under discussion. Current NCCN guideline recommend N1 patients to receive PMRT. This study aims to evaluate the impact of PMRT on different breast cancer subtype. Between 1990 and 2013, there were 1252 patients with Stage II breast cancer (T1-2 with one to three positive) treated by mastectomy at the Koo Foundation Sun Yat-Sen Cancer Center. We divided breast cancer into luminal (ER/PR+, HER2-), HER2 overexpressed, and triple negative subtype. Overall survival (OS) and disease-free survival (DFS) were calculated by Kaplan-Meier method. The median follow up time was 80 months. In this cohort, luminal, HER2 overexpressed, triple negative subtypes accounted for 59%, 28.4%,12.6%, respectively. Among them, 765 (61%) of patients were treated with PMRT. Survival analyses revealed that PMRT was significant improved 10 years OS and DFS in all subtypes except HER2 subtype (Table 1). The absolute 10-year survival gain was 8% in luminal subtype, and 25% in triple negative subtype. Further propensity score matching results are pending.Abstract TU_4_3360; Table 1Luminal, HER2 and triple negative breast cancer with or without PMRTNRadiotherapyDFSp valueOSP valueAll765Yes82%<0.00184%0.0043487No68%78%Luminal406Yes78%0.007887%0.0089332No72%79%HER2240Yes75%0.017378%0.5696116No67%76%Triple negative119Yes80%0.001989%0.005339No56%64% Open table in a new tab PMRT improved long term DFS in women with pT1-T2/N1 breast cancer in luminal and triple negative breast cancers.

Second primary squamous cell carcinoma in patients with nasopharyngeal carcinoma after radiotherapy-Predictors and prognostic factors.

We investigated risk and prognostic factors for second primary squamous cell carcinoma (SCC) in patients with nasopharyngeal carcinoma (NPC) after radiotherapy (RT). A total of 49021 patients with NPC were treated at Sun Yat-Sen Cancer Center between January 1970 and December 2009. The incidence and management of second primary SCCs were analyzed. A total of 142 patients (0.29%) developed second primary SCC, with 78.2% in the upper aerodigestive tract. Older age, smoking, and chemotherapy were associated with an increased rate of second primary SCC. The 3, 5, and 10-year overall survival (OS) rates for second primary SCC were 47.18%, 31.69%, and 11.97%, respectively. Advanced age, family history of cancer, and treatment modality were independent prognostic factors for survival. Second primary tumors rarely develop in patients with NPC treated with RT, but when this occurs, second primary SCC comprises a majority of these. Intensity-modulated RT may shorten the latency to second primary SCC. Surgery as the first-line treatment may improve survival and prognosis.

Elevated baseline serum lactate dehydrogenase indicates a poor prognosis in primary duodenum adenocarcinoma patients.

Purpose: Tumour cells produce energy through glycolysis and lactate dehydrogenase (LDH) is a key part of glycolysis. Elevation of serum LDH may indicate poor prognosis in primary duodenum adenocarcinoma. We aim to explore the prognostic significance of LDH in this disease.Methods and materials: Two hundred forty-four patients diagnosed with primary duodenum adenocarcinoma who were treated at the Sun Yat-sen Cancer Center from February 1996 to January 2016 were retrospectively analysed. We collected routine clinical data, including baseline LDH. Patients were classified into a normal LDH group (≤ 245U/L) and higher LDH group (>245U/L). Correlations of the LDH level and other clinicopathological characteristics were explored using the Chi-square test. Prognostic factors for overall survival were identified using univariate and multivariate analyses.Results: Two hundred seven patients (84.9%) had normal LDH levels, while 37 patients (15.1%) had abnormally high LDH levels. Higher LDH levels were significantly associated with more distant metastasis, node metastasis, poor differentiation and TNM stage Ⅲ-Ⅳ (P<0.05). Consistently, patients with node metastasis, poor differentiation and TNM stageⅢ-Ⅳ had a significantly higher median LDH level (P<0.05). The median survival of patients in the higher LDH group was significantly shorter than that of the patients in the normal LDH group (16.3 m vs. 42.5 m, P=0.02). Using multivariate analysis, LDH, age and radical surgery were independent prognostic factors associated with overall survival(OS) (HR=1.571, P=0.036 for LDH; HR=1.514, P=0.013 for age; HR=0.248, P<0.0001 for radical surgery, respectively).Conclusions: For the first time, our research suggests that baseline serum LDH is an independent prognostic factor in primary duodenum adenocarcinoma patients and elevated baseline serum LDH indicates a poor prognosis.

1054PD - A New Classification for Nasopharyngeal Carcinoma

Background: This study is to develop and validate a new classification for nasopharyngeal carcinoma (NPC). Methods: Fifteen hundred and twenty-eight (1528) newly diagnosed NPC patients treated between 1995 and 2010 were included in this study. Seven hundred and one patients (n = 701) were treated with 3D conformal radiotherapy (3D-RT) and 827 patients were treated with IMRT. Cox proportional hazards model was used to select the significant split node to partition patients into the different risk group. Recursive partitioning analysis derived a new classification in patients treated with 3D-RT objectively. This new staging system was then validated in patients treated with IMRT. Results: The median follow-up interval was 84.6 months (ranging 2-175 months). According to the 7th AJCC staging system, the stage I patients showed a 5-year overall survival (OS) rate of 93.0%, stage II of 94.5%, stage III of 87.5%, stage IVA of 71.5%, stage IVB of 61.3%, and stage IVC of 5.8% (p < 0.0001). In the validation group (n = 827), the Group I in new system was patients with stages of T1-3N0-1 and T1N2 (n = 364); their 5-year OS was 92.4%. The Group II was patients with stages of T2N2 and T3N2 (n = 175); thier 5-year OS was 86.0%. The Group III was patients with stages of any T4 and N3 (n = 249); their 5-year OS was 72.0%. The Group IV was patients with distant metastasis (n = 36); their 5-year OS was 17.9%. This new classification system will be compared to the 8th AJCC staging system. Conclusions: We propose a new staging system for NPC, which distributes more patients in the early stage.Table1054PD Patient Distribution According to Chinese 2008 and the 7th AJCC staging systemsStageChinese 2008 staging2010 AJCC stagingCurrent proposalStage I2.3%2.3%42.9%Stage II11.0%23.7%21.9%Stage III39.4%49.1%30.0%Stage IV47.3%24.9%5.2% Open table in a new tab Legal entity responsible for the study: None Funding: Koo Foundation Sun Yat-Sen Cancer Center Disclosure: All authors have declared no conflicts of interest.

Prognostic role of initial pan-endoscopic tumor length at diagnosis in operable esophageal squamous cell carcinoma undergoing esophagectomy with or without neoadjuvant concurrent chemoradiotherapy.

The objective of this study was to appraise the prognostic role of initial pan-endoscopic tumor length at diagnosis within or between operable esophageal squamous cell carcinoma (ESCC) undergoing upfront esophagectomy or neoadjuvant concurrent chemoradiotherapy (nCCRT) followed by esophagectomy. Between Jan 2001 and Dec 2013 in Koo-Foundation Sun Yat-sen Cancer Center in Taiwan, 101 ESCC patients who underwent upfront esophagectomy (surgery group) and 128 nCCRT followed by esophagectomy (nCCRT-surgery group) were retrospectively collected. Prognostic variables, including initial pan-endoscopic tumor length at diagnosis (sub-grouped ≤3, 3-5 and >5 cm), status of circumferential resection margin (CRM), and pathological T/N/M-status and cancer stage, were appraised within or between surgery and nCCRT-surgery groups. Within surgery group, longer initial pan-endoscopic tumor length at diagnosis (≤3, 3-5 and >5 cm; HR =1.000, 1.688 and 4.165; P=0.007) was an independent prognostic factor that correlated with advanced T/N/M-status, late cancer stage, and CRM invasion (all's P<0.001). Based on the initial pan-endoscopic tumor length at diagnosis ≤3, 3-5 and >5 cm, nCCRT-surgery group had a poorer (P=0.039), similar (P=0.447) and better (P<0.001) survivals than did surgery group, respectively. For those with initial pan-endoscopic tumor length at diagnosis >5 cm, nCCRT-surgery group had more percentage of T0/N0-status and stage 0 (all's P<0.05), and fewer rate of CRM invasion (P=0.036) than did surgery group. Initial pan-endoscopic tumor length at diagnosis could be a criterion to select proper ESCC cases for nCCRT followed by esophagectomy to improve survival and reduce CRM invasion.

304PD Treatment approach and prognosis of pediatric and adolescent non-epithelial malignant ovarian tumors: A retrospective prognosis analysis

Background Non-epithelial malignant ovarian tumors are rare in the pediatric and adolescent population. Because of the rarity of the disease, few studies with a large sample size are available, and survival and prognostic factors in this specific group of patients are poorly known. Methods This was a retrospective study of 170 girls (median age at presentation of 14 years) diagnosed with primary non-epithelial malignant ovarian tumors between 1990 and 2014 at the Sun Yat-sen Memorial Hospital and Cancer Center of Sun Yat-sen University. Symptoms, pathological data, treatments, and outcomes were obtained retrospectively from the medical records. Results Most (85.29%) tumors occurred in patients aged 10-18 years and most cases were FIGO stage I (70.0%). The predominant pathological type was germ cell tumors (87.06%). All patients underwent surgery, and 80 (47.06%) underwent conservative incomplete staging surgery (unilateral salpingo-oophorectomy or tumor excision). The 5-year progression-free survival (PFS) was 59.2%.The 5-year overall survival (OS) was 88.7%. Surgical hospital (HR = 0.388,95%CI=0.213-0.706, P = 0.002) was independently associated with PFS. Recurrence state (HR = 163.26,95%CI=1.321- 20181.875, P = 0.038) was independentlyassociatedwith OS. Conclusions Ovarian cancers in children and adolescents have features of good prognosis. Girls who received first operation in tertiary hospitals had better PFS. Patients who did not suffer recurrence had better OS. Legal entity responsible for the study Sun Yat-sen Memorial Hospital Funding N/A Disclosure All authors have declared no conflicts of interest.

Prevalence, risk factors, and the desire for help of distressed newly diagnosed cancer patients: A large-sample study.

Beginning in 2007, all newly diagnosed cancer patients at the Koo Foundation Sun Yat-Sen Cancer Center (KF-SYSCC) were screened for psychosocial distress. Our social workers, as part of the psychosocial care team (PCT), have engaged in proactive outreach with patients identified as distressed. The goal of the present study was to assess the prevalence of psychosocial distress and the extent of contact between the PCT and distressed patients. Newly diagnosed patients who were treated at KF-SYSCC between 2007 and 2010 for cancer were eligible if there were at least 100 patients with the same type of cancer. Before treatment began, they were screened with the Pain Scale and the Distress Thermometer (DT) and had the option to specify a desire for help. The rates of distress were analyzed by cancer type and by probable related factors. Information regarding contact with the PCT was retrieved from computerized databases. Overall, some 5,335 cancer patients representing 12 major cancer types were included in our study. Of these, 1,771 (33.20%) were significantly distressed. By multivariate logistic regression, younger age, female gender, higher pain score, and disease stage, but not cancer type, were found to be associated with higher rates of distress. Among these distressed patients, 628 (36%) had some contact with the PCT. This Taiwanese study with a large sample size revealed a prevalence rate of psychosocial distress similar to rates found in Western countries. Contact with the PCT was established in only 36% of significantly distressed patients, despite a proactive outreach program. It is very important to have screening results made available in a timely fashion to the psycho-oncology team so that appropriate care can be offered promptly.

Laparoscopic intracorporeal stapling of the gastric tube on the basis of surface blood supply after minimally invasive esophagectomy

Background/IntroductionMinimally invasive esophagectomy is a complex operation in which creating a healthy gastric substitute is crucial. The present study evaluated a novel method of reconstructing the intracorporeal laparoscopic gastric tube on the basis of surface blood supply to the stomach. PurposeTo study the feasibility and safety of a novel method of laparoscopic gastric tube reconstruction. MethodsAfter the complete mobilization of the stomach, the stomach was intracorporeally stapled along the watershed area between the blood supplies of the lesser and greater curvatures. Subsequently, the gastric tube was pulled up to the neck for end-to-side cervical esophagogastrostomy. Perioperative data were prospectively collected for the first 20 patients who had undergone this novel laparoscopic gastric reconstruction at our institute. The descriptive statistics are reported in this paper. ResultsWe enrolled 20 patients (18 men and 2 women) with esophageal cancer who were admitted to the Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan between January 2013 and December 2013. The mean operative time was 7.10 ± 1.08 hours, and the mean operative blood loss was 118.00 ± 79.71 mL. The average length of the gastric tubes above the sternal notch was 7.65 cm (∼5.0–15.0 ± 2.40 cm); the average width of the gastric tubes was 3.74 ± 0.47 cm. No case required conversion to open surgery, and only one patient (5%) experienced a minor anastomotic leak. The overall complication rate was 45% (predominantly involving postoperative transient hoarseness), and no surgical mortality was observed in this study. ConclusionTotal laparoscopic intracorporeal gastric tube reconstruction based on anatomical characteristics of the surface blood supply to the stomach is safe and feasible.

Long-term outcomes of modified Berlin–Frankfurt–Münster-90 regimen in adults with T-lymphoblastic lymphoma: a single-center experience

The standard treatment for adult T-Lymphoblastic lymphoma (T-LBL) has not been defined. This study was to analyze the efficiency of modified BFM-NHL-90 regimen in 36 adult patients with newly diagnosed T-LBL at the Sun Yat-Sen cancer center between August 2000 and December 2010. After the induction protocols, 34/36 (94%) of the patients achieved complete remission or unconfirmed complete remission. At the median follow-up of 36 months, 13 patients relapsed, but no relapses were observed in the CNS. The 3-year overall survival and 3-year event-free survival rates were 66.9% and 65.4%, respectively. Patients of female gender with hepatomegaly and hemoglobin less than 120 g/L, and the time interval exceeding 38 days between induction 1a and 1b, had inferior EFS and OS. The results was comparable to the previous regimens and the regimen could prevent CNS relapse with 4 high-dose MTX every 3 months during the maintenance phase.

Experiences with a simple laparoscopic gastric tube construction

BackgroundMinimally invasive esophagectomy (MIE) is a complex operation, and the detailed optimal surgical procedure has not been well described. Our aim was to evaluate use of a simple method of laparoscopic gastric tube construction as minimally invasive surgery for patients with esophageal cancer.MethodsWe performed a retrospective review of 26 consecutive patients who underwent MIE for esophageal cancer in the Koo Foundation Sun Yat-Sen Cancer Center between September 2009 and August 2011. Perioperative data and postoperative complications were statistically analyzed.ResultsThe patient group consisted of 22 men and 4 women. MIE was performed successfully in all patients. The mean operative time was 430.4 ± 60.6 minutes, and the mean estimated operative blood loss was 135.0 ± 97.8 mL. There were no cases of conversion to open surgery during the procedure. The postoperative complication rate was 53.8%, and there was no surgical mortality.ConclusionsWe recommend this novel method of total laparoscopic staplized formation of gastric tube to facilitate gastric pull-up.

Abstract P4-16-05: Benefit from Postoperative Radiotherapy for N1 Breast Cancer

Abstract Purpose: To evaluate the outcomes for patients with Stage II breast cancer and one to three positive lymph nodes after mastectomy who were treated with observation or adjuvant radiotherapy to the chest wall (CW) and regional lymphatics; and to identify a group of patients who benefit from postmastectomy radiotherapy (PMRT). Methods and Materials: The subjects were 716 patients diagnosed between 1990 and 2007 with Stage II breast cancer (one to three positive lymph nodes) treated with mastectomy at the Koo Foundation Sun Yat-Sen Cancer Center. 283 patients had undergone PMRT to the CW and regional lymphatics according to in-house treatment guideline or physician decision. Since 2003, we recommend PMRT for patients who had 2 or more risk factors; age less than 40 y/o, T2 disease, GrII/GrIII, prominent lymphovascular invasion (LVI), presence of extracapsular spreading (ECS), and negative Estrogen Receptor (ER(−)). Survival was analyzed by the Kaplan—Meier method. The survival free of isolated locoregional disease(LRR), metastasis free survival(MFS), disease free survival(DFS), and overall survival(OS) were analyzed according to the delivery of radiotherapy or not. Results: The median follow-up was 80 months. LRR, MFS, DFS and OS were significantly improved by PMRT. The 5- and 10-year LRR rate without PMRT was 89.9% and 81.6%, respectively and, with PMRT was 97.7% and 97.0% respectively (p &amp;lt;0.0001). The 5- and 10-year MFS rate without PMRT was 84.4% and 76.5%, respectively, and, with PMRT, was 90.8% and 87.2% respectively (p = 0.0153). The 5- and 10-year DFS rate without PMRT was 80.8% and 69.8%, respectively, and, with PMRT, was 89.6% and 86.1% respectively (p = 0.001). The 5- and 10-year OS rate without PMRT was 89.1% and 77.3%, respectively, and, with PMRT, was 94.6% and 86.2% respectively (p = 0.0039). 239 patients had less than 2 risk factors, their LRR, MFS and DFS did not benefit from PMRT. Conclusion: Our data suggest that adjuvant PMRT improve LRR, MFS, DFS and OS for stage II breast cancer with one to three positive lymph nodes who had 2 or more risk factors (Age less than 40 y/o, T2, GrII/GrIII, LVI, ECS, ER(−)). Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-16-05.

Short-term results of thoracoscopic lobectomy and segmentectomy for lung cancer in koo foundation sun yat-sen cancer center.

Thoracoscopic lobectomy and segmentectomy have been demonstrated to be safe and technically feasible for curative resection of lung cancer. This minimally invasive surgery is increasingly popular and adopted by the world all over. We report our short-term results of thoracoscopic lobectomy/segmentectomy operations comparing with previous surgical approach for lung cancer resection by muscle-sparing vertical minithoracotomy in Koo Foundation Sun Yat-Sen Cancer Center. We performed a retrospective review of 317 consecutive patients who underwent lobectomy or segmentectomy either by thoracoscopic surgery (n=121) or muscle-sparing vertical mini-thoracotomy (n=195) for lung cancer in Koo Foundation Sun Yat-Sen Cancer center between Jan 2000 and Jun 2009. The operative details, postoperative complication, and length of stay were statistically analyzed. Thoracoscopic lobectomy and segmentectomy were performed successfully in 121 patients. One patient was converted to open thoracotomy during operation due to uncontrolled bleeding. There is no significant difference in age factors (p=0.763), forced expiratory volume in one second (p=0.480) or comorbidities (p=0.549) between these two groups. Thoracoscopic group had a significantly predominant percentage in women, diabetes mellitus, less smoking index and chronic obstructive pulmonary disease incidence. Patients undergoing a thoracoscopic surgery had a shorter length of stay (6.8±3.4 vs. 10.2±9.1 days, p<0.001), longer operative time (3.6±1.0 vs. 3.2±1.2 hours, p=0.004), and less blood loss (102.7±95.7 vs. 140.1±171.2 ml, p<0.029). There was no significant difference in postoperative complication rate between the two groups (18.2% vs. 23.6%, p=0.255). No surgical mortality was found in the thoracoscopic group. Our findings suggested thoracoscopic surgery for lung cancer would be as safe as muscle-sparing vertical mini-thoracotomy in lobectomy and segmentectomy.

Overexpression of SGLT1 and EGFR in colorectal cancer showing a correlation with the prognosis

Na+-dependent glucose cotransporter (SGLT1), reported overexpression in tumor tissues while its clinical significance was not established, and epidermal growth factor receptor (EGFR) with potential relation to SGLT1 were studied in order to investigate their clinical significance in colorectal cancer (CRC). Eighty-five patients of CRC who received chemotherapy in Sun Yat-sen Cancer Center from March 1st 2005 to December 31st 2008 were enrolled. SGLT1 and EGFR expression in these cancer tissues and 28 normal tissues were tested by immunohistochemistry. (1) Expression of SGLT1 (P = 0.00) and EGFR (P = 0.01) in cancer tissues was higher than that in normal tissues. (2) Their expression related with clinical stage (P = 0.03 and P = 0.02), but not with other clinical characteristics. (3) For first-line chemotherapy, expression of SGLT1 (P = 0.06 and P = 0.21) and EGFR (P = 0.37 and P = 0.31) had no influence on objective response rate (ORR) and disease control rate (DCR). EGFR overexpression was associated with lower disease-free survival (P = 0.00) and overall survival (P = 0.01), while SGLT1 did not (P = 0.79 and P = 0.34). Conclusions Both SGLT1 and EGFR overexpression in CRC was related to higher clinical stages. SGLT1 had a potential impact on the ORR of first-line chemotherapy in CRC. EGFR was associated with prognosis, while SGLT1 did not.

Efficacy of cetuximab combined with chemotherapy for patients with advanced colorectal cancer and unclear K-ras status

To study the efficacy and safety of cetuximab combined with chemotherapy for patients with advanced colorectal cancer (ACRC) and unclear K-ras status. Clinical data of 102 ACRC patients, treated by cetuximab combined with chemotherapy in Sun Yat-sen Cancer Center from March 2005 to December 2008, were collected. The cumulative survival rate, objective response rate (ORR), disease control rate (DCR), progression free survival (PFS) of the cases were calculated. The difference in ORR, DCR, PFS and oval survival (OS) between the regimens used as first-line and non-first-line treatment, and between the regimens including oxaliplatin and irinotecan were compared. The overall ORR of cetuximab plus chemotherapy was 43.1%, DCR 73.5%, median PFS 4.0 months, OS 28.5 months, and the 1-year, 3-year, and 5-year survival rate was 89.2%, 50.9% and 27.5%, respectively. The differences in ORR (50.0% vs. 40.0%, P = 0.344), DCR (78.1% vs. 72.9%, P = 0.571) and OS (51.0 months vs. 35.0 months, P = 0.396) between the regimens as first line and as non-first line treatment were not statistically significant. However, the PFS of the regimen as first-line was longer than that as non-first-line treatment (PFS 5.5 months vs. 3.0 months, P = 0.001). The differences in ORR (54.2% vs. 40.0%, P = 0.223), DCR (79.2% vs. 74.7%, P = 0.654), PFS (5.0 months vs. 3.0 months, P = 0.726) and OS (36.0 months vs. 40.0 months, P = 0.759) between cetuximab plus oxliplatin and irinotecan were not statistically significant. The most common side effects of cetuximab plus chemotherapy were acneiform eruption (80.4%, grade 3-4 in 9.8%), neutropenia (66.7%, grade 3-4 in 18.6%), and diarrhea (19.6%, grade 3-4 in 5.9%). No treatment-related death was recorded. Patients with advanced colorectal cancer and unclear K-ras treated by cetuximab combined with chemotherapy have good ORR and OS, and the regimen is safe with less adverse events for them. There is no significant difference between the efficacies of regimens as first line and as non-first line treatment, and between cetuximab plus oxliplatin and cetuximab plus irinotecan regimens.

Relationship between the number of lymph node detection and prognosis in stage II gastric cancer after D(2) dissection

To explore the relationship between the lymph node count and prognosis in stage II gastric cancer. Retrospective analysis was performed for the 268 cases with gastric cancer who underwent parallel D(2) dissection between January 1990 and December 2006 in the Sun Yat-Sen Cancer Center. The Japanese Gastric Cancer Association(JGCA) 13th edition of pathological staging system was used to define stage II gastric cancer. Patients were followed up until December 2008. The Kaplan-Meier method and chi-square test were used for data analysis. All the data were analyzed using SPSS16.0 for Windows. The average number of detected lymph nodes was 17.3+/-1.2. There were 109 patients with detected lymph node <15. The 1-, 3-, and 5-year survival rates were 92.7%, 67.8%, and 50.9%, respectively. The number of detected lymph node was > or =15 in 159 cases, and the 1-, 3-, and 5-year survival rates were 96.9 %, 81.0%, and 66.4%, respectively. The difference between two groups was statistically significant (P=0.003). Further analysis of the 199 cases with no lymph node metastasis (pN(0) group) showed that there were 95 cases with lymph nodes <15, and the 1-, 3-, and 5-year survival rates were 92.6%, 70.4%, and 55.9%, respectively. There were 104 patients with > or =15 lymph nodes, and the 1-, 3-, and 5-year survival rates were 97.1%, 84.4%, and 66.8%, respectively. The difference was also statistically significant (P=0.049). There were 69 cases with lymph node metastasis (PN(1) group), and the 1-, 3-, and 5-year survival rates of 14 patients with lymph nodes <15 were 92.9%,57.1%, and 34.3%, respectively. Comparing two groups, the survival rate was significantly different (P=0.034). There were 55 patients with > or =15 lymph nodes, and the 1-, 3-, and 5-year survival rates were 96.4%, 73.4%, and 63.8%. The difference was statistically significant (P=0.036). In patients with stage II gastric cancer as defined by the JGCA 13th edition, the survival rate is better in patients with more than 15 detected lymph nodes as compared to those with less than 15.